Background: The systemic immune-inflammation index (SII) has been used as a prognostic marker for several cancer types, but there is no in-depth study in bladder cancer. This study evaluated the potential utility of the SII as a prognostic factor in patients with bladder cancer after radical cystectomy.Methods: A retrospective analysis of 209 patients with bladder cancer who had undergone radical cystectomy and were randomized into primary (N=139) and validation (N=70) cohorts was conducted. The overall survival (OS) was calculated using the Kaplan-Meier survival curves. The prognostic value of the SII in primary and validation cohorts were analyzed by using the Cox regression model. A SII-based nomogram for bladder cancer was produced in R software.Results: A high SII (>507) was associated with poor prognosis in bladder cancer patients. Univariate and multivariate analyses revealed that the SII was an independent predictor for OS. The SII emerged as an independent prognostic factor that provided more accurate prognostic prediction than neutrophillymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein/albumin ratio (CAR), in the primary and validation cohorts. The nomogram had better accuracy and discrimination than tumor, lymph node, metastasis (TNM) classification. The concordance index values of nomogram were 0.82 for the primary cohort and 0.784 for the validation cohort. Conclusions:The SII can serve as an independent predictor of OS in patients who have undergone radical cystectomy for bladder cancer, and was found to be a better predictor of prognosis than NLR, PLR, and CAR. The nomogram is a reliable model for predicting postoperative OS of patients after radical cystectomy.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme in tryptophan metabolism and plays an important role in tumor cell immunosuppression and angiogenesis. The molecular mechanisms of IDO1 and epithelial-mesenchymal transition (EMT) have not been elucidated or studied in bladder cancer. Therefore, the aims of this study were to detect IDO1 expression in bladder cancer tissues and then to investigate the role of IDO1 in bladder cancer cell EMT and malignant phenotypes as well as the underlying molecular mechanisms. By immunohistochemistry, Western blot, and quantitative reverse transcription–polymerase chain reaction experiments, IDO1 was found to be overexpressed in bladder cancer tissues and cell lines compared to the noncancerous ones. In addition, knockdown of IDO1 expression was shown to inhibit bladder cancer cell growth, migration, invasion, and EMT. Furthermore, we demonstrated that IDO1 may promote EMT by activation of the interleukin 6/signal transducer and activator of transcription 3/programmed cell death ligand 1 signaling pathway. Collectively, these data suggest that IDO1 may play an important role in bladder cancer and may be a novel therapeutic target for patients with bladder cancer.

Background: Metastasis is the primary cause of cancer deaths, warranting further investigation. This study assessed microRNA-153 (miR-153) expression in bladder cancer tissues and investigated the underlying molecular mechanism of miR-153-mediated regulation of bladder cancer cells. Methods: Paired tissue specimens from 45 bladder cancer patients were collected for qRT-PCR. The Cancer Genome Atlas (TCGA) dataset was used to identify associations of miR-153 with bladder cancer prognosis. Bladder cancer tissues and immortalized cell lines were used for the following experiments: miR-153 mimics and indoleamine 2,3-dioxygenase 1 (IDO1) siRNA transfection; Western blot, cell viability, colony formation, and Transwell analyses; nude mouse xenograft; and chicken embryo chorioallantoic membrane angiogenesis (CAM) assays. Human umbilical vein endothelial cells (HUVECs) were co-cultured with bladder cancer cells for the tube formation assay. The luciferase reporter assay was used to confirm miR-153-targeting genes. Results: miR-153 expression was downregulated in bladder cancer tissues and cell lines, and reduced miR-153 expression was associated with advanced tumor stage and poor overall survival of patients. Moreover, miR-153 expression inhibited bladder cancer cell growth by promoting tumor cell apoptosis, migration, invasion, and endothelial mesenchymal transition (EMT) in vitro and tumor xenograft growth in vivo , while miR-153 expression suppressed HUVEC and CAM angiogenesis. At the gene level, miR-153 targeted IDO1 expression and inhibited bladder cancer cell tryptophan metabolism through inhibiting IL6/STAT3/VEGF signaling. Conclusions: Collectively, our data demonstrate that miR-153 exerts anti-tumor activity in bladder cancer by targeting IDO1 expression. Future studies will investigate miR-153 as a novel therapeutic target for bladder cancer patients.